This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. RNA silencing is an ancient RNA-based immune response, which is conserved from fission yeast to human beings. In order to anti-virus infection, host uses structural unique small RNAs to pair with the infected virus mRNAs for degradation. However, virus itself has produced diversified RNA silencing suppressors to counter anti-virus response during millions years evolution. The main goal of this proposal is to study this counter-interaction between the host and virus evolved by nature selection at the molecular level. Project 1 Structural Basis for dsRNA Recognition by NS1 protein of Human Influenza Virus A Influenza A viruses are important human pathogens resulting in periodic pandemic threaten, while NS1 protein of influenza A virus (NS1A) shields the virus against host defense. We plan to solve the complex strcuture of Ns1A/siRNA duplex. Project 2 Structural basis for RNA-silencing suppression by Tomato aspermy virus protein 2b 2b protein encoded by cucumovirus functions as post-transcriptional gene silencing (PTGS) suppressor to counter host defense during infection. We plan to solve the complex structure of Tav2b/siRNA duplex.